Protein identification is an important problem in many proteomics projects, including studies of post-translational modifications, protein-protein interactions, and protein functions. This grant proposal focuses on the computational aspect of tandem mass spectrometry (MS-MS), a technology of choice in many proteomics projects. Computational analysis is often a bottleneck in applying this technology for protein identification since the corresponding combinatorial problems remain largely unsolved. In close collaboration with leading mass-spectrometry groups we propose to develop new algorithms and software for identification of mutated and modified proteins, de-novo protein sequencing, DXMS, and gene validation via mass-spectrometry. We also propose to implement MS-ALIGNMENT, MS-SEQUENCING, and MS-GENESEARCH software tools as a web server available for mass-spectrometry researchers.